Activation of Poly(ADP-Ribose) Polymerase by Sulfur Mustard in Hela Cell Cultures
Abstract
Poly(ADP-ribose) polymerase (PADPRP) E.C.2.4.2.30 has been proposed to play a key role in the NAD+ depletion following alkylation of DNA in sulfur mustard (HD) exposures. Papirmeister et al. (Fundam Appl Toxicol 5:Sl34, 1985) hypothesized that activation of PADPRP was central to the subsequent depletion of NAD+ and activation of proteolytic enzymes leading to vesication. NAD+ depletion following HD exposure has been previously documented and the results have been used to infer the effect of HD exposure on PADPRP. The present study was undertaken to demonstrate the direct effect of HD on PADPRP activity. HeLa cells culture were used as the model system. At 10 microns HD PADPRP activity was increased above the levels of controls in the first hour. The activity peaked at 4 hrs and by 6 hrs had returned to control levels. The 24-hour level of PADPRP activity was again elevated above the controls. The 100 microns HD exposures had maximal enzymatic response in HeLa cells within the first hour. The level had decreased 40% from the maximum by the second hour reaching a plateau at 30% of the maximum response after 4 hrs. Cells exposed to 100 microns HD showed enzyme levels at or below those seen with the 10 microns dose after 24 hours. The doses of HD used did not decrease viability as measured by trypan blue dye exclusion within 24 hr.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008773
Entities
People
- Offie E. Clark
- William J. Smith
Organizations
- United States Army Medical Research Institute of Chemical Defense